The purpose of this new, reorganized Core is to provide physics, optical imaging and spectroscopy, and mathematical modeling support for the PPG. In so doing, we anticipate that new methods and approaches will be developed in close connection to the specific aims of the 5 individual projects. Optics is of course a critical element of PDT, and optical dosimetry has been a theme of the Core from the beginning. The new scientific emphasis of the Core builds on the realization that there are significant opportunities to exploit advances in biomedical optics within the context of preclinical and clinical PDT. Because of its long tradition of bringing PDT from the laboratory to the clinic, Roswell Park Cancer Institute (RPCI) is perhaps uniquely situated in the United States to make breakthroughs in this area. Exciting opportunities exist on several levels. For example, the lesions treated by PDT are necessarily optically accessible, and this enables integration of optical spectroscopic monitoring with the delivery of PDT. The photosensitizers used in PDT fluoresce, and this renders them directly detectable via fluorescence imaging in cells and in vivo. Advances in molecular imaging strategies have made it possible to image therapy-induced gene expression, tumor and normal tissue vasculature, and host cell responses to treatment in vivo at subcellular resolution. Important advances in understanding the various factors that contribute to the microscopic deposition of photodynamic dose have led to the development of new and very powerful mathematical models of PDT dosimetry, which have the capability of informing and being informed by ongoing and planned clinical trials. An additional important role for the Core is to continue to provide outstanding technical support for the preclinical and clinical laser and fiber delivery systems that are integral to each of the projects. The specific aims of the Optical Spectroscopy, Molecular Imaging, and Dosimetry Modeling Core are: 1) To continue to provide technical and scientific support for the clinical instrument that integrates PDT delivery with fluorescence and reflectance spectroscopy; 2) To develop in vivo molecular imaging methods in close connection to all projects; 3) To utilize a new model of microscopic PDT dosimetry to inform the design and interpretation of clinical trials; and 4) To provide routine engineering and optics support for the clinical and preclinical research efforts of the PPG.